Description: (Applicant's Description) Objectives: 1) The measurement of prodrugs and activated drugs from in-vitro assays and in samples of brain tumor, plasma and other tissues. This CORE has been strongly affiliated with Projects 1 and 4 over the prior three years. During the five years of funding requested, this CORE will provide measurements of metabolites of CPA, CPT-11 from tissue culture systems and rodent models whether the prodrugs are activated by herpes vectors or herpes-based amplicons. 2) Evaluation of the interaction of the effects of CPA and CPT-11. This CORE will provide the pharmacologic basis for the scheduling and mode of administration of drug combinations for the MGH-2 vector system. 3) To provide biodegradable polymers containing prodrugs for implantation in animals for local prodrug delivery. As in prior years, Dr. Ludeman will construct CPA and CPT-11 polymer systems for implantation into rodent brains. Contractual arrangements will be made for GMP polymers in human studies. 4) Studies of drug resistance in transfected tumor cells. Tumor cells from rodents will be examined for scavenger enzyme, mismatched repair enzymes.